Various environmental and industrial chemicals can perturb male reproductive function. The objectives of these studies are to define subcellular target sites in testicular somatic cells in primary culture. For FY90, efforts have focused on effects of mono(2-ethylhexyl)phthalate, and the active metabolite of tri-ocresyl phosphate (TOCP), saligenin cyclic o-tolyl phosphate, on Sertoli cells in primary culture. Efforts with saligenin have focused on identifying molecular changes in exposed Sertoli cells. Gel electrophoresis and phosphorylation studies are underway to examine changes in phosphorylation patterns seen after exposure to saligenin. With regard to MEHP, we have shown that it not only specifically inhibits FSH-induced cAMP accumulation in cultured Sertoli cells but that it has a site of action distal to cAMP formation since it inhibits 8 bromo cAMP induced estradiol secretion. We have also found that the action of MEHP on cultured Sertoli cell cAMP accumulation, in contrast to its action in vivo, are not age-dependent. Thus, further studies are needed to define the site and mechanism of action of MEHP on testicular function.
